SMN2
| Survival of motor neuron 2, centromeric | |||||||||||||
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 PDB rendering based on 1g5v. | |||||||||||||
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| Identifiers | |||||||||||||
| Symbols | SMN2 ; BCD541; C-BCD541; GEMIN1; SMNC; TDRD16B | ||||||||||||
| External IDs | OMIM: 601627 MGI: 109257 HomoloGene: 292 GeneCards: SMN2 Gene | ||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 6607 | 20595 | |||||||||||
| Ensembl | ENSG00000172062 | ENSMUSG00000021645 | |||||||||||
| UniProt | Q16637 | P97801 | |||||||||||
| RefSeq (mRNA) | NM_017411 | NM_001252629 | |||||||||||
| RefSeq (protein) | NP_059107 | NP_001239558 | |||||||||||
| Location (UCSC) | Chr 5: 69.35 – 69.37 Mb | Chr 13: 100.12 – 100.14 Mb | |||||||||||
| PubMed search | |||||||||||||
Survival of motor neuron 2, centromeric also known as SMN2 is a protein which in humans is encoded by the SMN2 gene.[1][2]
Gene
This gene is part of a 500 kb inverted duplication on chromosome 5q13. This duplicated region contains at least four genes and repetitive elements which make it prone to rearrangements and deletions. The repetitiveness and complexity of the sequence have also caused difficulty in determining the organization of this genomic region. The telomeric and centromeric copies of this gene are nearly identical and encode the same protein. While mutations in the telomeric copy are associated with spinal muscular atrophy, mutations in this gene, the centromeric copy, do not lead to disease. This gene may be a modifier of disease caused by mutation in the telomeric copy. The critical sequence difference between the two genes is a single nucleotide in exon 7, which is thought to be an exon splice enhancer. Note that the nine exons of both the telomeric and centromeric copies are designated historically as exon 1, 2a, 2b, and 3-8. It is thought that gene conversion events may involve the two genes, leading to varying copy numbers of each gene.[2]
Function
The full length protein encoded by this gene localizes to both the cytoplasm and the nucleus. Within the nucleus, the protein localizes to subnuclear bodies called gems which are found near coiled bodies containing high concentrations of small ribonucleoproteins (snRNPs). This protein forms heteromeric complexes with proteins such as SIP1 and GEMIN4, and also interacts with several proteins known to be involved in the biogenesis of snRNPs, such as hnRNP U protein and the small nucleolar RNA binding protein. Four transcript variants encoding distinct isoforms have been described.[2]
See also
References
- ↑ Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, Benichou B, Cruaud C, Millasseau P, Zeviani M (January 1995). "Identification and characterization of a spinal muscular atrophy-determining gene". Cell 80 (1): 155–65. doi:10.1016/0092-8674(95)90460-3. PMID 7813012.
- ↑ 2.0 2.1 2.2 "Entrez Gene: survival of motor neuron 2, centromeric".
Further reading
- Watihayati MS, Fatemeh H, Marini M et al. (2009). "Combination of SMN2 copy number and NAIP deletion predicts disease severity in spinal muscular atrophy.". Brain Dev. 31 (1): 42–5. doi:10.1016/j.braindev.2008.08.012. PMID 18842367.
- Prior TW, Krainer AR, Hua Y et al. (2009). "A positive modifier of spinal muscular atrophy in the SMN2 gene.". Am. J. Hum. Genet. 85 (3): 408–13. doi:10.1016/j.ajhg.2009.08.002. PMC 2771537. PMID 19716110.
- Coady TH, Baughan TD, Shababi M et al. (2008). Valcarcel, Juan, ed. "Development of a single vector system that enhances trans-splicing of SMN2 transcripts.". PLoS ONE 3 (10): e3468. doi:10.1371/journal.pone.0003468. PMC 2565107. PMID 18941511.
- Elsheikh B, Prior T, Zhang X et al. (2009). "An analysis of disease severity based on SMN2 copy number in adults with spinal muscular atrophy.". Muscle Nerve 40 (4): 652–6. doi:10.1002/mus.21350. PMID 19760790.
- Workman E, Saieva L, Carrel TL et al. (2009). "A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice.". Hum. Mol. Genet. 18 (12): 2215–29. doi:10.1093/hmg/ddp157. PMC 2685758. PMID 19329542.
- Bose JK, Wang IF, Hung L et al. (2008). "TDP-43 overexpression enhances exon 7 inclusion during the survival of motor neuron pre-mRNA splicing.". J. Biol. Chem. 283 (43): 28852–9. doi:10.1074/jbc.M805376200. PMC 2661999. PMID 18703504.
- Hauke J, Riessland M, Lunke S et al. (2009). "Survival motor neuron gene 2 silencing by DNA methylation correlates with spinal muscular atrophy disease severity and can be bypassed by histone deacetylase inhibition.". Hum. Mol. Genet. 18 (2): 304–17. doi:10.1093/hmg/ddn357. PMC 2638778. PMID 18971205.
- Corcia P, Camu W, Praline J et al. (2009). "The importance of the SMN genes in the genetics of sporadic ALS.". Amyotroph Lateral Scler 10 (5-6): 436–40. doi:10.3109/17482960902759162. PMID 19922137.
- Tiziano FD, Pinto AM, Fiori S et al. (2010). "SMN transcript levels in leukocytes of SMA patients determined by absolute real-time PCR.". Eur. J. Hum. Genet. 18 (1): 52–8. doi:10.1038/ejhg.2009.116. PMC 2987170. PMID 19603064.
- Jedrzejowska M, Milewski M, Zimowski J et al. (2009). "Phenotype modifiers of spinal muscular atrophy: the number of SMN2 gene copies, deletion in the NAIP gene and probably gender influence the course of the disease.". Acta Biochim. Pol. 56 (1): 103–8. PMID 19287802.
- Arkblad E, Tulinius M, Kroksmark AK et al. (2009). "A population-based study of genotypic and phenotypic variability in children with spinal muscular atrophy.". Acta Paediatr. 98 (5): 865–72. doi:10.1111/j.1651-2227.2008.01201.x. PMID 19154529.
- Paushkin S, Gubitz AK, Massenet S, Dreyfuss G (2002). "The SMN complex, an assemblyosome of ribonucleoproteins.". Curr. Opin. Cell Biol. 14 (3): 305–12. doi:10.1016/S0955-0674(02)00332-0. PMID 12067652.
- Farooq F, Balabanian S, Liu X et al. (2009). "p38 Mitogen-activated protein kinase stabilizes SMN mRNA through RNA binding protein HuR.". Hum. Mol. Genet. 18 (21): 4035–45. doi:10.1093/hmg/ddp352. PMID 19648294.
- Hasanzad M, Golkar Z, Kariminejad R et al. (2009). "Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy.". Ann. Acad. Med. Singap. 38 (2): 139–41. PMID 19271042.
- Martins de Araújo M, Bonnal S, Hastings ML et al. (2009). "Differential 3' splice site recognition of SMN1 and SMN2 transcripts by U2AF and U2 snRNP.". RNA 15 (4): 515–23. doi:10.1261/rna.1273209. PMC 2661831. PMID 19244360.
- Song F, Qu YJ, Zou LP et al. (2008). "[Molecular analysis of survival motor neuron gene in 338 suspicious children patients with spinal muscular atrophy]". Zhonghua Er Ke Za Zhi 46 (12): 919–23. PMID 19134255.
- Irimura S, Kitamura K, Kato N et al. (2009). "HnRNP C1/C2 may regulate exon 7 splicing in the spinal muscular atrophy gene SMN1.". The Kobe journal of medical sciences 54 (5): E227–36. PMID 19628962.
- Yong J, Wan L, Dreyfuss G (2004). "Why do cells need an assembly machine for RNA-protein complexes?". Trends Cell Biol. 14 (5): 226–32. doi:10.1016/j.tcb.2004.03.010. PMID 15130578.
- Chen HH, Chang JG, Lu RM et al. (2008). "The RNA binding protein hnRNP Q modulates the utilization of exon 7 in the survival motor neuron 2 (SMN2) gene.". Mol. Cell. Biol. 28 (22): 6929–38. doi:10.1128/MCB.01332-08. PMC 2573304. PMID 18794368.
- Cogulu O, Durmaz B, Pehlivan S et al. (2009). "Evaluation of the SMN and NAIP genes in a family: homozygous deletion of the SMN2 gene in the fetus and outcome of the pregnancy.". Genet Test Mol Biomarkers 13 (3): 287–8. doi:10.1089/gtmb.2008.0139. PMID 19397406.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.